RESUMEN

Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8+ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

Asunto(s)

Inmunoterapia , Linfocitos Infiltrantes de Tumor , Monoaminooxidasa , Microambiente Tumoral , Macrófagos Asociados a Tumores , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Masculino , Femenino , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Persona de Mediana Edad , Anciano , Inmunoterapia/métodos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/efectos de los fármacos , Monoaminooxidasa/metabolismo , Anciano de 80 o más Años , Neoplasias Vesicales sin Invasión Muscular

RESUMEN

AIM: Primary Signet Ring Cell Carcinoma (SRCC) of the bladder accounts for only 1%‒4% of all bladder malignancies. To date, few studies have been conducted to investigate the characteristics of SRCC. This study aimed to investigate the clinical features and treatments of SRCC and explore the independent risk factors of survival in SRCC patients. PATIENTS AND METHODS: A retrospective study was conducted on 32 eligible patients. The survival rate was calculated with the Kaplan-Meier method, and the COX proportional hazards model was used to investigate the independent risk factors of prognosis. RESULTS: In the present study, the 1-year and 2-year survival rates of SRCC patients were 53.1% and 9.4%, respectively. The TNM stage, tumor differentiation, and metastasis after treatment were risk factors for the prognosis of SRCC patients (p < 0.05), while surgical treatment, chemotherapy, and positive GATA3 expression were protective for prognosis (p < 0.05). Multivariate analysis showed that GATA3 was an independent protective factor for prognosis (p < 0.05), and T-stage was an independent risk factor (p < 0.05). CONCLUSIONS: Primary SRCC of the bladder is highly malignant and has a poor prognosis. Its clinical and imaging findings are usually non-specific. Early radical cystectomy and postoperative adjuvant systemic chemotherapy are helpful to improve the survival rate. T-stage is an independent risk factor for survival, and positive GATA3 expression is protective for primary SRCC of the bladder.

Asunto(s)

Carcinoma de Células en Anillo de Sello , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Factores de Riesgo , Adulto , Estadificación de Neoplasias , Estimación de Kaplan-Meier , Pronóstico , Tasa de Supervivencia , Modelos de Riesgos Proporcionales , Anciano de 80 o más Años

RESUMEN

OBJECTIVES: To evaluate the safety and effectiveness of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC), and open radical cystectomy (ORC) in bladder cancer. METHODS: A literature search for network meta-analysis was conducted using international databases up to February 29, 2024. Outcomes of interest included baseline characteristics, perioperative outcomes and oncological outcomes. RESULTS: Forty articles were finally selected for inclusion in the network meta-analysis. Both LRC and RARC were associated with longer operative time, smaller amount of estimated blood loss, lower transfusion rate, shorter time to regular diet, fewer incidences of complications, and fewer positive surgical margin compared to ORC. LRC had a shorter time to flatus than ORC, while no difference between RARC and ORC was observed. Considering lymph node yield, there were no differences among LRC, RARC and ORC. In addition, there were statistically significant lower transfusion rates (OR=-0.15, 95% CI=-0.47 to 0.17), fewer overall complication rates (OR=-0.39, 95% CI=-0.79 to 0.00), fewer minor complication rates (OR=-0.23, 95% CI=-0.48 to 0.02), fewer major complication rates (OR=-0.23, 95% CI=-0.68 to 0.21), fewer positive surgical margin rates (OR=0.22, 95% CI=-0.27 to 0.68) in RARC group compared with LRC group. CONCLUSION: LRC and RARC could be considered as a feasible and safe alternative to ORC for bladder cancer. Notably, compared with LRC, RARC may benefit from significantly lower transfusion rates, fewer complications and lower positive surgical margin rates. These data thus showed that RARC might improve the management of patients with muscle invasive or high-risk non-muscle invasive bladder cancer.

Asunto(s)

Cistectomía , Laparoscopía , Tempo Operativo , Procedimientos Quirúrgicos Robotizados , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/efectos adversos , Cistectomía/métodos , Cistectomía/estadística & datos numéricos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Laparoscopía/estadística & datos numéricos , Metaanálisis en Red , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Reproducibilidad de los Resultados , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/cirugía

RESUMEN

OBJECTIVE: We present a novel technique to perform single-port (SP) robot-assisted partial cystectomy with excision of the urachal remnant and bilateral pelvic lymph node dissection for urachal adenocarcinoma (1-7). MATERIALS AND METHODS: A 41-year-old male presented to the clinic for multiple episodes of hematuria and mucousuria. Office cystoscopy revealed a small solitary tumor at the dome of the bladder, with a diagnostic bladder biopsy revealing a tubule-villous bladder adenoma. Cross-sectional imaging of the chest/abdomen/pelvis revealed a 4.5 cm cystic mass arising from the urachus without evidence of local invasion and metastatic spread. He underwent SP robotic-assisted partial cystectomy with excision of the urachal remnant and bilateral pelvic lymph node dissection. Surgical steps include: 1) peritoneal incision to release the urachus and drop bladder 2) identification of urachal tumor 3) intraoperative live cystoscopic identification of bladder mass and scoring of tumor margins using Toggle Pro feature 4) tumor excision with partial cystectomy 5) cystorrhaphy 6) bilateral pelvic lymph node dissection 7) peritoneal interposition flap to mitigate lymphocele formation. RESULTS: Surgery was successful, with no intraoperative complications, an operative time of 100 minutes, and estimated blood loss of 20 mL. The patient was discharged on post-op day one, and the Foley catheter removed one week after surgery. Final pathology revealed a 7.5 cm infiltrating urachal muscle-invasive adenocarcinoma of the bladder (pT2b). Negative surgical margins were achieved. CONCLUSIONS: Single-port robot-assisted partial cystectomy for urachal adenocarcinoma is safe and can achieve equivalent oncologic outcomes to the standard of care with minimally invasive and open techniques.

Asunto(s)

Adenocarcinoma , Cistectomía , Escisión del Ganglio Linfático , Procedimientos Quirúrgicos Robotizados , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Procedimientos Quirúrgicos Robotizados/métodos , Cistectomía/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Adulto , Escisión del Ganglio Linfático/métodos , Resultado del Tratamiento , Tempo Operativo , Reproducibilidad de los Resultados

RESUMEN

The Bacillus Calmette-Guérin (BCG) vaccine is the oldest cancer immunotherapeutic agent in use. Despite its effectiveness, its initial mechanisms of action remain largely unknown. Here, we elucidate the earliest cellular mechanisms involved in BCG-induced tumor clearance. We developed a fast preclinical in vivo assay to visualize in real time and at single-cell resolution the initial interactions among bladder cancer cells, BCG and innate immunity using the zebrafish xenograft model. We show that BCG induced the recruitment and polarization of macrophages towards a pro-inflammatory phenotype, accompanied by induction of the inflammatory cytokines tnfa, il1b and il6 in the tumor microenvironment. Macrophages directly induced apoptosis of human cancer cells through zebrafish TNF signaling. Macrophages were crucial for this response as their depletion completely abrogated the BCG-induced phenotype. Contrary to the general concept that macrophage anti-tumoral activities mostly rely on stimulating an effective adaptive response, we demonstrate that macrophages alone can induce tumor apoptosis and clearance. Thus, our results revealed an additional step to the BCG-induced tumor immunity model, while providing proof-of-concept experiments demonstrating the potential of this unique model to test innate immunomodulators.

Asunto(s)

Apoptosis , Vacuna BCG , Macrófagos , Transducción de Señal , Neoplasias de la Vejiga Urinaria , Pez Cebra , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/inmunología , Animales , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Vacuna BCG/farmacología , Vacuna BCG/uso terapéutico , Transducción de Señal/efectos de los fármacos , Humanos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Microambiente Tumoral

RESUMEN

BPV-2 infection can cause bladder infections in cattle that, when associated with bracken fern consumption, can progress to cancerous bladder tumors and also present as bovine enzootic hematuria (BEH). This study aimed to evaluate the prolonged natural BPV-2 infection in the blood and urine of cattle, excluding bracken fern consumption. Thirteen Girolando papillomatosis-affected cattle with no bracken fern contact history were monitored for 20 months. Blood, urine, and wart samples were collected for BPV-2 detection and clinical laboratory analyses. All animals showed the presence of BPV-2 in papillomas and blood, and 92.85% showed BPV-2 in urine, suggesting viral dissemination in the urinary tract. Despite all animals being infected with BPV-2, none showed BEH signs during the study. Thus, it was observed that BPV-2 infection alone didn't induce BEH over 20 months, implying a complex interaction with environmental factors or genetic predisposition. This underlines bracken fern consumption's critical role in urinary bladder carcinogenesis. The study underscores BEH's pathogenesis complexity, advocating longitudinal studies to comprehend BPV-2's role fully.

Asunto(s)

Enfermedades de los Bovinos , Papiloma , Infecciones por Papillomavirus , Animales , Bovinos , Enfermedades de los Bovinos/orina , Enfermedades de los Bovinos/virología , Enfermedades de los Bovinos/sangre , Infecciones por Papillomavirus/veterinaria , Infecciones por Papillomavirus/orina , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/virología , Papiloma/veterinaria , Papiloma/virología , Papiloma/orina , Papiloma/sangre , Femenino , Masculino , Pteridium , Neoplasias de la Vejiga Urinaria/veterinaria , Neoplasias de la Vejiga Urinaria/orina , Neoplasias de la Vejiga Urinaria/sangre

RESUMEN

Solasonine (SS) and solamargine (SM) are alkaloids known for their antioxidant and anticancer properties, which can be further enhanced by encapsulating them in nanoparticles. This led to a study on the potential therapeutic benefits of SS and SM against bladder cancer when encapsulated in lipid-polymer hybrid nanoparticles (LPHNP). The LPHNP loaded with SS/SM were prepared using the emulsion and sonication method and their physical-chemical properties characterized. The biological effects of these nanoparticles were then tested in both 2D and 3D bladder cancer cell culture models, as well as in a syngeneic orthotopic mouse model based on the MB49 cell line and ethanol epithelial injury. The LPHNP-SS/SM had an average size of 130 nm, a polydispersity index of 0.22 and a positive zeta potential, indicating the presence of chitosan coating on the nanoparticle surface. The dispersion of LPHNP-SS/SM was found to be monodispersed with a span index of 0.539, as measured by nanoparticle tracking analysis (NTA). The recrystallization index, calculated from DSC data, was higher for the LPHNP-SS/SM compared to LPHNPs alone, confirming the presence of alkaloids within the lipid matrix. The encapsulation efficiency (EE%) was also high, with 91.08 % for SS and 88.35 % for SM. Morphological analysis by AFM and Cryo-TEM revealed that the nanoparticles had a spherical shape and core-shell structure. The study showed that the LPHNP-SS/SM exhibited mucoadhesive properties by physically interacting with mucin, suggesting a potential improvement in interaction with mucous membrane. Both the free and nanoencapsulated SS/SM demonstrated dose-dependent cytotoxicity against bladder cancer cell lines after 24 and 72 h of treatment. In 3D bladder cell culture, the nanoencapsulated SS/SM showed an IC50 two-fold lower than free SS/SM. In vivo studies, the LPHNP-SS/SM displayed an antitumoral effect at high doses, leading to a significant reduction in bladder volume compared to the positive control. However, there were observed instances of systemic toxicity and liver damage, indicated by elevated levels of transaminases (TGO and TGP). Overall, these results indicate that the LPHNPs effectively encapsulated SS/SM, showing high encapsulation efficiency and stability, along with promising in vitro and in vivo antitumoral effects against bladder cancer. Further evaluation of its systemic toxicity effects is necessary to ensure its safety and efficacy for potential clinical application.

Asunto(s)

Lípidos , Nanopartículas , Alcaloides Solanáceos , Neoplasias de la Vejiga Urinaria , Animales , Nanopartículas/química , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Línea Celular Tumoral , Lípidos/química , Alcaloides Solanáceos/administración & dosificación , Alcaloides Solanáceos/química , Alcaloides Solanáceos/farmacología , Polímeros/química , Ratones , Humanos , Femenino , Portadores de Fármacos/química , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Ratones Endogámicos C57BL

RESUMEN

Equine bladder neoplasms are rare. This report aimed to describe the clinical signs and treatment of urothelial carcinoma (UC) in a mule. Cystoscopy of a 20-year-old female mule with a one-week history of hematuria and anemia revealed vascular congestion in the mucosa and an intraluminal, pedunculated mass in the dorsal bladder region. Histopathological examination revealed UC. Initial therapy consisted of four weekly cystoscopic guided injections of fluorouracil. At the fourth chemotherapy session, a paler and more friable tumor mass was observed. Consequently, we opted to surgically remove it during cystoscopy. Following mass excision, patient comfort, gross appearance of urine, and the hematocrit returned to normal. Repeat cystoscopy examinations revealed no gross appearance of tumor recurrence 18 months after treatment. Bladder neoplasms clinically resemble urolithiasis and cystitis and should be considered a differential diagnosis in cases of anemia and hematuria.

Asunto(s)

Neoplasias de la Vejiga Urinaria , Femenino , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia , Animales , Carcinoma/diagnóstico , Carcinoma/patología

RESUMEN

OBJECTIVE: Our study aimed to evaluate the impact of bacillus Calmette-Guérin shortage on recurrence and progression in patients with non-muscle invasive bladder cancer in a Brazilian cohort. METHODS: We retrospectively reviewed the clinicopathological data of 409 patients who had their first transurethral resection of the bladder tumor for intermediate or high-risk non-muscle invasive bladder cancer between June 2014 and May 2021 in a tertiary public hospital in Brazil. Patients included had non-muscle-invasive urothelial carcinoma of the bladder resected completely for the first time, regardless of bacillus Calmette-Guérin use. Low-risk disease patients were excluded from the analysis. Demographic, clinicopathological, and bacillus Calmette-Guérin use data were collected from our database. Recurrence and progression data were obtained from patient records or through telephone interviews. Recurrence-free survival and progression-free survival were calculated from the date of transurethral resection of the bladder tumor until the events of recurrence, progression, last office visit, or phone interview. RESULTS: Within a median follow-up period of 26.7 months, 168 (41.1%) patients experienced a recurrence in a median time of 27 months (95%CI 16.1-38). Bacillus Calmette-Guérin was administered to 57 (13.9%) individuals after transurethral resection of the bladder tumor. Patients with ≥3 lesions (p<0.001), those with lesions >3 cm (p=0.02), and those without bacillus Calmette-Guérin treatment (p<0.001) had shorter recurrence-free survival. According to a Cox multivariate regression model, bacillus Calmette-Guérin use was independently associated with a reduced recurrence rate, with an HR of 0.43 (95%CI 0.25-0.72). Out of the patients studied, 26 (6.4%) experienced progression. T1 stage (p<0.001) and high-grade (p<0.001) were associated with shorter progression-free survival. Bacillus Calmette-Guérin did not influence bladder cancer progression. In the Cox multivariate analysis, high-risk disease was independently associated with progression (p<0.001). CONCLUSION: Our study confirms that non-muscle invasive bladder cancer exhibits a high recurrence rate. The use of adjuvant bacillus Calmette-Guérin in intermediate and high-risk patients significantly reduces this rate. Furthermore, the bacillus Calmette-Guérin shortage could have negatively impacted these patients.

Asunto(s)

Vacuna BCG , Recurrencia Local de Neoplasia , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Masculino , Vacuna BCG/uso terapéutico , Femenino , Estudios Retrospectivos , Brasil/epidemiología , Anciano , Persona de Mediana Edad , Factores de Riesgo , Adyuvantes Inmunológicos/uso terapéutico , Progresión de la Enfermedad , Administración Intravesical , Anciano de 80 o más Años , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía

RESUMEN

BACKGROUND: Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is associated with significant morbidity and mortality. We present an alternative technique that preserves the complete mesenteric vascularization during the isolation of the intestinal segment used in ICUD, including distal vessels. This approach aims to minimize the risk of ischemia in both the ileal anastomosis and the isolated loop at the diversion site. METHODS: This cohort study included 31 patients, both male and female, who underwent RARC with ICUD from February 2018 to November 2023, performed by a single surgeon. Intraoperative and postoperative complications data were retrieved for analysis, employing our proposed mesentery-sparing technique in all cases. The primary endpoint was the incidence of intraoperative and postoperative complications directly attributable to the mesentery-sparing approach in ICUD. Secondary endpoints included other postoperative variables not directly related to mesentery preservation, such as the incidence of postoperative ileus requiring parenteral nutrition and the duration of hospitalization. RESULTS: None of the patients experienced intraoperative or postoperative complications directly related to mesentery-sparing, such as intestinal fistulae or internal hernias. The median duration of hospitalization was 6 days, and postoperative ileus necessitating total parenteral nutrition occurred in 19% of the patients. Minor complications (Clavien-Dindo grades I-II) accounted for 27.6% of the cases and major complications (grades III-V) accounted for 20.6%. CONCLUSION: The mesentery-sparing technique outlined herein offers an alternative method for preserving the vascularization of intestinal segments and reducing the risk of intestinal complications in ICUD during RARC.

Asunto(s)

Cistectomía , Mesenterio , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Robotizados , Derivación Urinaria , Humanos , Cistectomía/métodos , Femenino , Masculino , Procedimientos Quirúrgicos Robotizados/métodos , Derivación Urinaria/métodos , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/prevención & control , Mesenterio/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Tratamientos Conservadores del Órgano/métodos , Resultado del Tratamiento , Complicaciones Intraoperatorias/prevención & control , Estudios Retrospectivos , Reproducibilidad de los Resultados , Estudios de Cohortes

RESUMEN

OBJECTIVE: To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. MATERIALS AND METHODS: The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. RESULTS: Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. CONCLUSION: The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

Asunto(s)

Enfermedades Autoinmunes , Ciclofosfamida , Cistitis , Mesna , Neoplasias de la Vejiga Urinaria , Humanos , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Cistitis/prevención & control , Mesna/uso terapéutico , Mesna/administración & dosificación , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Vasculitis Sistémica/complicaciones , Vasculitis Sistémica/tratamiento farmacológico , Brasil , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Hemorragia/inducido químicamente , Sociedades Médicas , Reumatología

RESUMEN

BACKGROUND: Bladder cancer (BC) is the seventh most common cancer worldwide. Not every infection ends as cancer, although the HPV-induced carcinogenesis is a complex process consequence of inflammation. To determine the association between human papillomavirus (HPV) and the diagnosis of bladder cancer. METHODS: We carried out a systematic review according to Cochrane and PRISMA recommendations. We searched in EMBASE, Medline (Ovid), and The Cochrane Central Register of Controlled Trials (CENTRAL), from inception to nowadays. We included case-control studies. The risk of bias assessment was performed based on QUADAS2. We performed a random effect Meta-analysis. RESULTS: We included 14 studies in qualitative and quantitative analysis. There was mainly a low risk of bias. We finally found a strong association between the presence of HPV and bladder cancer diagnosis (OR 4.18 95%CI 2.63-6.66; I2 = 40%). CONCLUSIONS: HPV is currently associated with the diagnosis of bladder cancer.

Asunto(s)

Infecciones por Papillomavirus , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/virología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/complicaciones , Papillomaviridae , Estudios de Casos y Controles , Virus del Papiloma Humano

RESUMEN

Bladder cancer (BC) is the 10th most common cancer worldwide, with about 0.5 million reported new cases and about 0.2 million deaths per year. In this scoping review, we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines. We searched PubMed, CENTRAL, Embase, and supplemented with manual searches through the Scopus, and Web of Science for published studies until February 2023. We included original studies that used at least one single-cell technology to study bladder cancer. Forty-one publications were included in the review. Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy. Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples. The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level. Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management. This nascent tool can advance the early diagnosis, prognosis judgment, and targeted therapy of bladder cancer.

Asunto(s)

Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Pronóstico , Microambiente Tumoral/genética

RESUMEN

OBJECTIVE: To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants. METHODS: Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes. RESULTS: A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66 years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77 months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8 months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14 months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93). CONCLUSIONS: In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy.

Asunto(s)

Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Femenino , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/patología , Cistectomía , Estudios Retrospectivos , Brasil , Medición de Riesgo

RESUMEN

Introducción: El cáncer de la vejiga es uno de los más frecuentes del tracto urinario y se manifiesta de dos formas: como tumor superficial de bajo grado o como neoplasia invasora de alto grado. Objetivo: Caracterizar el cáncer vesical en adultos, según variables clínicas, epidemiológicas y de servicio. Métodos: Se realizó un estudio observacional descriptivo y retrospectivo, para caracterizar el cáncer vesical en adultos, según variables clínicas, epidemiológicas y de servicio de los pacientes atendidos en el servicio de Urología del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro» en el periodo comprendido de octubre 2019 y 2022. Población del estudio: 242 pacientes diagnosticados con cáncer vesical. Resultados: La mayoría de los pacientes diagnosticados con cáncer vesical corresponden al año 2019 (45,86 %): masculinos (75,20 %); blancos (89,25 %); mayores de 70 o más años (64,46 %) y fumadores (95,45 %). La hematuria fue el síntoma principal (91,73 %), como expresión del carcinoma urotelial papilar de bajo grado (36,77 %). Tratamiento: la resección transuretral (88,01 %), sin metástasis a distancia (88,42 %). Conclusiones: La mayoría de los pacientes diagnosticados con cáncer vesical corresponden al año 2019, masculinos, blancos, mayores de 70 o más años, fumadores y con hematuria. Más frecuente: el carcinoma urotelial papilar de bajo grado. El tiempo trascurrido antes del diagnóstico de la enfermedad fue de 36-40 días, y un mes, el tiempo trascurrido antes del tratamiento de la enfermedad.

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Introduction: bladder cancer is one of the most frequent cancers of the urinary tract and manifests itself in two ways: as a superficial low-grade tumor or as a high-grade invasive neoplasm. Objective: to characterize bladder cancer in adults according to clinical, epidemiological and service variables. Methods: a descriptive and retrospective observational study was carried out to characterize bladder cancer in adults according to clinical, epidemiological and service variables of patients treated in the Urology service at "Arnaldo Milián Castro" Clinical and Surgical University Hospital from October 2019 and 2022. The study population was 242 patients diagnosed with bladder cancer. Results: most of the patients diagnosed with bladder cancer correspond to the year 2019 (45.86%): male (75.20%); whites (89.25%); older than 70 or more years (64.46%) and smokers (95.45%). Hematuria was the main symptom (91.73%), as an expression of low-grade papillary urothelial carcinoma (36.77%). The treatment was transurethral resection (88.01%), without distant metastasis (88.42%). Conclusions: most of the patients diagnosed with bladder cancer correspond to the year 2019, male, whites, older than 70 years or older, smokers and with hematuria. Low-grade papillary urothelial carcinoma was the most frequent cancer. The time elapsed before the diagnosis of the disease was 36-40 days, and the time elapsed before the treatment of the disease was 1 month.

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Neoplasias de la Vejiga Urinaria , Epidemiología , Gravedad del Paciente

RESUMEN

PURPOSE: To retrospectively evaluate the tislelizumab-based chemoimmunotherapy combined with gemcitabine/cisplatin for bladder-sparing in patients with muscle-invasive bladder cancer (MIBC). METHODS: Forty-five patients who received bladder-sparing treatment or radical cystectomy (RC) for MIBC (cT2-T4a, NxM0) were retrospectively enrolled. All patients received maximal transurethral resection of bladder tumor (mTURBT), followed by four cycles of chemo-immunotherapy with tislelizumab (PD-L1 inhibitor), gemcitabine, and cisplatin. Clinical efficacy was evaluated to compare the benefit of bladder-sparing treatment on clinical CR (cCR) and RC for non-cCR patients. The primary outcomes were bladder intact disease-free survival (BIDFS) and overall survival (OS), and the secondary outcomes were adverse effects. The PD-L1 status and molecular subtypes of tumors were analyzed. RESULTS: The overall survival rate was 88.8% (95%CI: 79.6%, 98.0%) at 12 months, 85.7% (95%CI: 74.9%, 96.5%) at 18 months, and 66.6% (95%CI: 45.2%, 88.0%) at 24 months. Twenty-nine patients (64.4%) achieved cCR and their OS rate was 96.6% (95%CI: 89.9%, 100%). Sixteen patients were in the non-cCR group, and their OS rate was 75.0% (95%CI: 53.8%, 96.2%) at 12 months, 65.6% (95%CI: 40.3%, 90.9%) at 18 months, and 52.5% (95%CI: 21.9%, 83.1%) at 24 months. The BIDFS rate for patients who received bladder-sparing treatment was 96.0% (95%CI: 88.4%, 100%) from 12 to 24 months. Four patients (8.8%) were PD-L1 positive and 41 patients (91.2%) were PD-L1 negative. CONCLUSIONS: Our retrospective study of patients with MIBC suggests that tislelizumab-based neoadjuvant therapy was a safe and effective bladder-sparing treatment.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Cistectomía , Desoxicitidina , Gemcitabina , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Anciano , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Tratamientos Conservadores del Órgano/métodos , Tasa de Supervivencia , Adulto , Anciano de 80 o más Años

RESUMEN

BACKGROUND: The ectopic pelvic kidney, a common renal anomaly, is often smaller and malformed, with a shorter and sometimes tortuous ureter (1). Muscle-invasive bladder cancer (MIBC), constituting 15-25% of bladder cancer cases (2), mandates radical cystectomy with a 50% 5-year survival rate (2). Despite the growing use of robot-assisted radical cystectomy (RARC) (3, 4), there is limited data on its application in ectopic kidneys. Only one RARC case has been reported (5), in contrast to numerous open radical cystectomies (1, 6) involving an ectopic kidney. PATIENT AND METHODS: After being diagnosed with T2 high-grade urothelial carcinoma, the 66-year-old patient, previously treated with multiple transurethral resections and adjuvant BCG therapy, received neoadjuvant chemotherapy. Preoperative staging CT revealed a 2.6 x 2.2 cm bladder neoformation and an ectopic right pelvic kidney. RESULTS: Using the da Vinci Surgical System, radical cystectomy with ileal conduit (sec Wallace II) and lymphadenectomy were performed. During the demolition phase, the shorter right ureter was dissected with care to avoid damage to the renal pedicle. The reconstructive phase included intracorporeal urinary diversion (ICUD) and uretero-ileal anastomosis, facilitated by the favorable position of the kidney. The 8-hour console surgery resulted in minimal blood loss. Discharged on day 16 due to COVID-19, the patient exhibited positive outcomes. A 2-month CT follow-up revealed no cancer recurrence, metastasis, hydronephrosis, and complete regression of the lymphocele. Imaging follow-up continues without postoperative adjuvant chemotherapy. CONCLUSION: Robotic surgery with intracorporeal urinary diversion holds potential for right-sided pelvic kidney cases, but additional studies are necessary for validation.

Asunto(s)

Carcinoma de Células Transicionales , Robótica , Neoplasias de la Vejiga Urinaria , Derivación Urinaria , Humanos , Anciano , Cistectomía , Estudios de Factibilidad , Neoplasias de la Vejiga Urinaria/cirugía , Recurrencia Local de Neoplasia , Riñón/cirugía

RESUMEN

PURPOSE: Smoking is a recognized risk factor for bladder BC and lung cancer LC. We investigated the enduring risk of BC after smoking cessation using U.S. national survey data. Our analysis focused on comparing characteristics of LC and BC patients, emphasizing smoking status and the latency period from smoking cessation to cancer diagnosis in former smokers. MATERIALS AND METHODS: We analyzed data from the National Health and Examination Survey (2003-2016), identifying adults with LC or BC history. Smoking status (never, active, former) and the interval between quitting smoking and cancer diagnosis for former smokers were assessed. We reported descriptive statistics using frequencies and percentages for categorical variables and median with interquartile ranges (IQR) for continuous variables. RESULTS: Among LC patients, 8.9% never smoked, 18.9% active smokers, and 72.2% former smokers. Former smokers had a median interval of 8 years (IQR 2-12) between quitting and LC diagnosis, with 88.3% quitting within 0-19 years before diagnosis. For BC patients, 26.8% never smoked, 22.4% were active smokers, and 50.8% former smokers. Former smokers had a median interval of 21 years (IQR 14-33) between quitting and BC diagnosis, with 49.3% quitting within 0-19 years before diagnosis. CONCLUSIONS: BC patients exhibit a prolonged latency period between smoking cessation and cancer diagnosis compared to LC patients. Despite smoking status evaluation in microhematuria, current risk stratification models for urothelial cancer do not incorporate it. Our findings emphasize the significance of long-term post-smoking cessation surveillance and advocate for integrating smoking history into future risk stratification guidelines.

Asunto(s)

Cese del Hábito de Fumar , Neoplasias de la Vejiga Urinaria , Adulto , Humanos , Encuestas Nutricionales , Fumar/efectos adversos , Neoplasias de la Vejiga Urinaria/etiología , Pulmón

RESUMEN

Urothelial carcinoma is a significant global health concern that accounts for a substantial part of cancer diagnoses and deaths worldwide. The tumor microenvironment is a complex ecosystem composed of stromal cells, soluble factors, and altered extracellular matrix, that mutually interact in a highly immunomodulated environment, with a prominent role in tumor development, progression, and treatment resistance. This article reviews the current state of knowledge of the different cell populations that compose the tumor microenvironment of urothelial carcinoma, its main functions, and distinct interactions with other cellular and non-cellular components, molecular alterations and aberrant signaling pathways already identified. It also focuses on the clinical implications of these findings, and its potential to translate into improved quality of life and overall survival. Determining new targets or defining prognostic signatures for urothelial carcinoma is an ongoing challenge that could be accelerated through a deeper understanding of the tumor microenvironment.

Asunto(s)

Carcinoma de Células Transicionales , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Carcinoma de Células Transicionales/patología , Transducción de Señal , Matriz Extracelular/patología , Matriz Extracelular/metabolismo , Células del Estroma/patología , Neoplasias Urológicas/patología

RESUMEN

Bladder cancer (BC) is one of the most common types of cancer worldwide, with significant differences in survival depending on the degree of muscle and surrounding tissue invasion. For this reason, the timely detection and monitoring of the disease are important. Surveillance cystoscopy is an invasive, costly, and uncomfortable procedure to monitor BC, raising the need for new, less invasive alternatives. In this scenario, microRNAs (miRNAs) represent attractive prognostic tools given their role as gene regulators in different biological processes, tissue expression, and their ease of evaluation in liquid samples. In cancer, miRNA expression is dynamically modified depending on the tumor type and cancer staging, making them potential biomarkers. This review describes the most recent studies in the last five years exploring the utility of miRNA-based strategies to monitor progression, stratify, and predict relevant clinical outcomes of bladder cancer. Several studies have shown that multimarker miRNA models can better predict overall survival, recurrence, and progression in BC patients than traditional strategies, especially when combining miRNA expression with clinicopathological variables. Future studies should focus on validating their use in different cohorts and liquid samples.

Asunto(s)

MicroARNs , Neoplasias de la Vejiga Urinaria , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Perfilación de la Expresión Génica/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología